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Biomedical subjects

A Granata

Publications and source records attributed to A Granata.

At least 37 records · Page 2Linked to original sources
PubMed1992

Characterization of a family with moderate hypercholesterolemia and binding defective low density lipoprotein.

Familial defective apolipoprotein B-100 (FDB) is a genetic disorder presenting with hypercholesterolemia and abnormal low density lipoprotein (LDL) that binds poorly to LDL receptors. This disease appears to be caused by a mutation in the apo B gene. In the present study thirteen members of a family with moderate hypercholesterolemia (250-350 mg/dl) were investigated. Biochemical studies on cultured skin fibroblasts ruled out classical familial hypercholesterolemia (receptor deficiency). LDL from nine affected members displayed, in an "in vitro" cell binding assay, a reduced affinity (2.5 fold) for the receptor, and had normal electrophoretic mobility, size and chemical composition. Lp(a) levels in family members were comparable to those present in normolipidemics and lower than those observed in primary hypercholesterolemia. The disorder is transmitted over three generations as an autosomal codominant trait and all the affected members are heterozygotes and hypercholesterolemic.

Adolescent↗
PubMed1992

Testosterone and erectile function, nocturnal penile tumescence and rigidity, and erectile response to visual erotic stimuli in hypogonadal and eugonadal men.

Further evidence that nocturnal erections are androgen-dependent and erectile responses to visual erotic stimuli are androgen-independent is presented from six men with secondary hypogonadism and six eugonadal controls. Erections during sleep were substantially less in the hypogonadal men, in terms of both tumescence and rigidity. In response to visual erotic stimuli, the percentage increase in circumference over baseline and the increase in rigidity were similar for the two groups.

Adult↗
PubMed1992

Low density lipoprotein receptor activity is modulated by soybean globulins in cell culture.

The effects of major storage globulins from soybean on cholesterol homeostasis were investigated in vitro and in vivo systems. The low density lipoprotein (LDL) uptake and degradation was studied both in human skin fibroblasts (HSF) and in a human hepatoma cell line (Hep G2). In Hep G2 cells a dose-dependent increase of both uptake and degradation of 125I-LDL was induced by the 7S globulin, whereas the 11S globulin exerted a lesser effect that was not dose-related. In HSF cells the 11S globulin increased the uptake of 125I-LDL to a greater extent than did 7S globulin; in this cell line, LDL degradation was not stimulated by either of the globulins. Rats fed a casein-cholesterol diet were treated daily with the 11S or 7S globulins for 2 wk. The administration of soybean globulins significantly reduced cholesterolemia (-35 and -34% with 7S and 11S globulins, respectively, vs. controls). Liver membrane preparations from the casein-cholesterol-fed rats showed a nonsignificant increase in the maximal binding of labeled cholesterol-rich lipoprotein fraction (beta-VLDL) to high affinity receptors.

Animals↗
PubMed1992

Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein-receptor interaction.

We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with beta-galactosidase-apoB fusion proteins spanning different areas of the apoB-100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor.

Antibodies, Monoclonal↗
PubMed1992

[Colonic radiography by double-contrast enema in the elderly patient with the use of trimebutine maleate].

About 15% of hospitalizations of patients over 65 are due to disorders of the colon which means that accurate analysis of history and clinical and instrumental investigation are mandatory. Our attention has been focused on x-ray examination using a double-contrast enema which, together with endoscopy, permits to diagnose colonic disorders with significant reliability. Our aim was to adapt the method to the special needs of the patient over 65 by employing the active substance trimebutine maleate (M.T.) as a "contact" pressure-lowering agent. Thirty-five subjects aged 65-75 with pathologies implying a risk for the use of parasympatholytic agents were examined. None of these patients showed side effects. It can therefore be said that the use of M.T. as a hypotonic agent in double-contrast enemas is an indisputable diagnostic aid.

Aged↗
PubMed1991

Familial defective apo B-100, characterization of an Italian family.

Familial defective apolipoprotein (apo) B-100 is a genetic disorder presenting with hypercholesterolaemia and abnormal low-density lipoprotein (LDL) that binds poorly to LDL receptors. This disease appears to be caused by a mutation in the apo B-100 gene. In the present study thirteen members of a family with moderate hypercholesterolaemia (250-350 mg dl-1) were investigated. Biochemical studies on cultured skin fibroblasts ruled out classical familial hypercholesterolaemia (FH, receptor deficiency). We then studied the interaction between LDL and their receptors by an in vitro cell binding assay. LDL from nine affected members displayed a reduced affinity (2.5-fold) for the receptor, and were less effective than LDL from control and unaffected members in suppressing LDL receptor expression and in stimulating cholesterol esterification. LDL from the affected members had normal electrophoretic mobility, size and chemical composition. Partial delipidation did not modify the LDL binding defect. The disorder is transmitted over three generations as an autosomal codominant trait and all the affected members are heterozygotes and hypercholesterolaemics. Analysis of DNA from family members showed a point mutation leading to an Arg to Gln substitution at amino acid 3500 of the mature protein that segregated with hypercholesterolaemia and LDL defective binding. We conclude that this family is affected by familial defective apolipoprotein B-100 (FDB).

Adolescent↗
PubMed1991

Sex hormone binding globulin, cortisol binding globulin, thyroxine binding globulin, ceruloplasmin: changes in treatment with two oral contraceptives low in oestrogen.

It is generally assumed that the oral contraceptives cause the carrier proteins to change. Notoriously this effect is used to evaluate indirectly their estrogenicity/gestagenicity ratio. In order to assess the residual intrinsic androgenic activity of two new 19-nor-derivative components, Desogestrel (DG) 150 micrograms and Gestodene (GD) 75 micrograms, both in association with Ethinylestradiol (EE) 30 micrograms, Sex Hormone Binding Globulin, Thyroxine Binding Globulin, Ceruloplasmin and Free Androgen Index (FAI), were studied in 40 young normally cycling healthy volunteers, matched for body mass index and age. The participants were randomly assigned to either EE-DG or EE-GD treatment. A marked significant increase in all the carrier proteins was found. Conversely, the values for FAI decreased significantly. The changes in the two groups were substantially of the same magnitude. These results are an indirect confirmation of the well-known negligible receptor binding affinity of the two progestogen in vitro, also supporting for these compounds the lack of relevant androgenic effects.

Carrier Proteins↗
PubMed1991

Changes in the plasma levels of proteins C and S in young women on low-dose oestrogen oral contraceptives.

The physiological importance of proteins C and S as natural anticoagulants is demonstrated by the increased risk of thromboembolic disease among subjects with hereditary deficiency of both proteins. In the present study the effects were evaluated of low-dose oestrogen oral contraceptives (OC) on the plasma levels of immunological protein S, as free (PS-f), and in reversible complex with C4b-binding protein as well as functional protein C (PC) in a homogeneous group of 20 young healthy women. The participants were randomly given either gestodene (75 micrograms) or desogestrel (150 micrograms) in combination with ethinyl oestradiol (30 micrograms). Blood samples were taken prior to the initiation of the treatment and at the end of the sixth 21-day treatment cycle. The mean concentration of both free and bound PS fell significantly, the decrease still being within the reference range. Conversely, the plasma values for PC rose to a statistically significant extent. There were no significant differences between the two OCs. Hypothetically, the changes in PS-f (active fraction) might be conducive to a procoagulant state, which the increased PC may compensate. The reverse effect of two OCs on the activity of the protein C-protein S anticoagulant system might suggest a different regulation of their synthesis.

Adult↗
PubMed1989

Monoclonal antibody 5A binds apolipoprotein B-48 and inhibits the low density lipoprotein-receptor interaction.

In a panel of 10 monoclonal antibodies raised against human LDL we detected three antibodies (named 5A, 6B, and 6E) which recognize both apolipoprotein B-100 and B-48. Antibody 5A inhibited, in a dose dependent manner, the interaction of 125I-LDL with their receptor on human skin fibroblasts. Using thrombolytic fragments, the epitope of antibody 5A was mapped to the carboxy terminal region of apo B-48. MAB 5A was equipotent with MAB Mb 47, an inhibitory antibody whose epitope lies near a putative receptor binding domain of apo B in thrombolytic fragment T2. These findings suggest that areas other than the carboxy terminal portion of apo B-100 may participate in the LDL-receptor interaction, either directly or by determining the exposition of high affinity sites of apo B-100.

Antibodies, Monoclonal↗
PubMed1988

Progesterone modulates the expression of HDL binding sites in human skin fibroblasts.

The aim of this work was to study the effects of progesterone on the expression of high density lipoprotein binding sites by cultured human skin fibroblasts. At concentrations ranging between 10(-6)- and 10(-4) M the hormone showed a dose-dependent induction of the HDL binding sites. The effect was maximal at 48 h. The increased HDL binding was only due to an up-regulation of binding sites, without changes of the apparent Kd. This effect was not related to changes of cellular cholesterol content, and was not affected by inhibition of protein synthesis. These data suggest that the expression of binding sites for HDL can be modulated via a mechanism that does not depend upon cellular cholesterol content.

Binding Sites↗
PubMed1988

Effect of derivatives of trapidil on the expression of LDL receptors.

The influence of trapidil and some of its derivatives (AR 12456, AR 12463, AR 12465) on the LDL receptor mediated uptake and degradation of 125 I-LDL by human skin fibroblasts (HSF) and human hepatic cells (HEP G2) was investigated. AR 12456 enhanced the uptake and degradation of 125 I-LDL in HEP G2, but inhibited this pathway in HSF. When this drug was preincubated with HEP G2 cells, and then the incubation medium was transferred to HSF, a stimulation of specific LDL pathway occurred also in this cell line. Trapidil, AR 12463 and AR 12465 were inactive under the same experimental conditions. These findings suggest that a metabolite of AR 12456 might be responsible for the enhanced expression of LDL receptors in human cells.

Antihypertensive Agents↗
PubMed1988

[Incidence of the so-called minor pollens in the Naples area].

The data concerning 2500 allergic patients are analysed and the low incidence of so-called "minor pollens" in respiratory allergopathies is documented. Moreover a frequent association of positivity with the so-called "major allergens" (Grass, Parietaria, Dermatophagoides) was observed. Specific hyposensitizing therapy is advised only in carefully selected patients, those showing perfect agreement between allergological data and clinical symptomatology.

Adolescent↗
PubMed1987

Abnormalities in pituitary thyroid axis function tests in patients with paroxysmal supraventricular arrhythmias.

The study was carried out on 60 consecutive patients (23 males and 37 females) aged between 20 and 83 years (means +/- SD, 40.7 +/- 16) who arrived at our Cardiologic Unit with paroxysmal supraventricular arrhythmias (PSVA) including junctional paroxysmal tachycardia (n = 32), atrial fibrillation (n = 13), atrial flutter (n = 1), premature beats (n = 13) and with no obvious cardiovascular causes. Serum thyroxine and triiodothyronine were normal in all patients and thyroid scintiscan revealed normal shape and size thyroids without autonomously functioning nodule(s). Thyrotropin (TSH) response to thyrotropin releasing hormone (TRH) was normal in 44 subjects in whom normal serum free T4 (FT4) and free T3 (FT3) levels were measured. Six patients with normal FT4 and FT3 levels did not respond to TRH. Abnormalities in thyrotropin response to TRH were observed in 10 patients all exhibiting increased FT4 or also FT3 levels. Among these, 5 patients did not respond to TRH, whereas the remaining 5 exhibited a blunted TSH response to TRH. These results suggest that only in a small proportion (5/60) of consecutive patients with PSVA it is possible to recognize a status of "occult thyrotoxicosis" on the basis of the combined evaluation of free thyroid hormones and TSH response to TRH.

Adult↗
PubMed1986

Calcium antagonists and low density lipoproteins metabolism by human fibroblasts and by human hepatoma cell line HEP G2.

The effect of Ca2+ antagonists (CA) on the receptor-mediated low density lipoprotein pathway has been investigated "in vitro" in human skin fibroblasts (HSF) and in human hepatoma cell line Hep G2. The specific binding and internalization of human 125I-labeled LDL are dose-dependently increased in HSF by CA of the verapamil series (verapamil, anipamil, gallopamil, ronipamil, and diltiazem), but neither by CA of the dihydropyridine series (nifedipine, nitrendipine) nor by flunarizine. BAY K 8644, a Ca2+ agonist, elicited an opposite effect. In the presence of the tested CA, LDL degradation is either unaffected (lower concentrations) or inhibited (higher concentrations). 125I-LDL uptake is stimulated also in fibroblasts from type IIa hypercholesterolemic patients, heterozygous for defective expression of LDL receptor. The enhanced cellular uptake of 125I-LDL was prevented by cycloheximide and by alpha-amanitin. CA of the verapamil series including diltiazem retained their effect in human hepatoma cell line Hep G2, a model proposed for hepatic metabolism of LDL. Our studies show that a) CA stimulate the high affinity binding and internalization of LDL in HSF and in human hepatoma cell line Hep G2; b) this stimulation involves DNA transcription and new protein synthesis; c) this effect is specific to one subgroup of Ca2+ antagonists (the verapamil class only).

Amanitins↗
PubMed1986

Behavior of preovulatory markers in normal and abnormal cycles.

Various ovulation markers in natural cycle (ultrasound measurement of follicular diameter, E2, progesterone, and LH assays) have been studied in 18 women. The patients were divided into two groups. Group 1: women who became pregnant during the same cycle; group 2: women who showed evidence of follicular growth, E2 and a LH midcycle rise, but low P levels in the luteal phase. A weaker increase in these parameters was found in group 2, especially the LH rise. Moreover, an asynchronicity between the endocrinological and morphological events has been observed in the suboptimal cycles. These findings suggest a process of follicular atresia at the end of the maturation phase, as is commonly found in otherwise normal women.

Female↗
PubMed1984

Long-standing recurrent paroxysmal supraventricular tachycardia disappearing after cystic degeneration of an episodically hypersecreting toxic adenoma of the thyroid.

A 35-year-old woman with an otherwise normal heart had been suffering from recurrent paroxysmal supraventricular tachycardia during the past 3 years. Serum thyroid function tests were repeatedly normal. When a thyroid nodule became evident, a toxic adenoma was diagnosed. Serum total hormone values were normal, but a few hours after the last recurrence of paroxysmal supraventricular tachycardia, total T3, free T3 and free T4 became clearly elevated. At that time hemorrhagic necrosis of the adenoma, though localized only at the periphery of the tumor, heavily impaired nodule overactivity, as judged by the disappearance of paroxysmal supraventricular tachycardia, by normal free thyroid hormone levels and by the return of a normal TSH response to TRH.

Adenoma↗